DESCRIPTION: (adapted from the abstract) The particular thrust of this proposal is to study the effect of diabetic conditions (elevated glucose and fatty acid) on ion transport in control and mesenteric arteries from streptozotocin-treated rats (IDDM) and obese Zucker (NIDDM) rats and the appropriate controls. Tissues from control and experimental animals will be incubated under such conditions and it is hypothesized that diabetic tissue will have altered properties. In addition, when the two tissues are incubated in the diabetic versus control conditions, the decrease in the glycolytic flux and glucose oxidation, and the increase in fatty acid oxidation, the inhibited ATPase activity, the increased sodium, calcium influx and increased vascular responses to vasoactive agents will all be magnified in diabetic vascular smooth muscles. The overall hypothesis of this proposal is that the pattern of substrate utilization is altered in diabetic VSM and that these disturbances in metabolism alter ion transport, leading to enhanced vascular reactivity. The effects of both normal and diabetic substrate conditions will be tested in these animals, with the suggestion that altered metabolism will lead to altered ion transport, and, in turn, to altered contractility.